ASCO: Vandetanib Fails to Prolong Progression-Free Small-Cell Lung Cancer

CHICAGO, June 5 -- Targeted therapy missed the mark as maintenance therapy for small-cell lung cancer (SCLC), researchers reported here.

In a small randomized trial, vandetanib (Zactima), an investigational dual-action drug that targets receptors for both epidermal growth and vascular endothelial growth factor, showed no efficacy as maintenance therapy for SCLC, the researchers said at the American Society of Clinical Oncology meeting.

In the trial, 107 patients who had responded to chemotherapy took 300 mg of vandetanib following completion of standard treatment. They had a median progression-free survival of 2.7 months versus 2.8 months for control patients, said Andrew M. Arnold, M.B.B.S., of the Juravinski Cancer Center in Hamilton, Ontario.

Dr. Arnold said it was the first randomized controlled trial of a VEGF inhibitor in small cell lung cancer.

Although the results were disappointing, he noted that the regimen selected-maintenance therapy following completion of platinum-based chemotherapy and radiation-may not have been the best test of an anti-VEGF agent in SCLC.

While accrual was under way, a team of French researchers reported benefit in a small series of SCLC patients who received 100 mg of thalidomide concurrently with chemotherapy. "So it may be that the drug would be effective if given concurrently," he said.

Moreover a planned subgroup analysis revealed that patients with limited disease appeared to benefit from vandetanib therapy (P=0.01) in contrast to patients with extended disease and there was also a suggestion of benefit for women, but Dr. Arnold cautioned that "the numbers were very small."

Timing also hindered the Canadian trial. It began accrual in May 2003, just as the SARS epidemic hit Toronto. "So accrual was very slow and the sample size was adjusted down to account for that difficulty," he said. Accrual was completed in March 2006.

All patients had demonstrated a complete or partial response to platinum-based therapy and had completed radiotherapy, which made them candidates for maintenance therapy, he said.

Among the findings:

• Vandetanib patients were more likely to develop prolonged QT interval and/or hypertension.
• Vandetanib was also associated with rash, diarrhea, and elevated liver enzymes.
• Fatigue was reported by 79% of vandetanib patients and 85% of control patients.
• Overall survival was 10.6 months in the vandetanib patients versus 11.9 months in the control patients.

"What we can conclude from this trial is that platinum-based chemotherapy and radiation therapy remain the gold standard treatments for small cell lung cancer," Dr. Arnold said.

Moreover, future trials of targeted therapy in SCLC should be "designed as concurrent treatment," he said.

Dr. Arnold disclosed no conflicts.